Hereditary hemochromatosis (HH) is a common disease characterized by excess iron deposition in the major organs of the body (Dadone, M. M. et al. AM. J. Clin. Pathol. 78:196-207 (1982); Edwards, C. Q. et al. N. Engl. J. Med. 18:1355-1362. (1988); McLaren, C. E., et al. Blood 86:2021-2027 (1995); Bothwell, T. H. et al., The metabolic and molecular basis of inherited disease (ed. C. R. Scriver, E.A.) 2237-2269 (McGraw-Hill, New York, 1995); Bacon, B. R. et al., Hepatology. A textbook of liver disease (eds. Zakim, D. & Boyer, T. D.) 1439-1472 (W.B. Saunders, Philadelphia, 1996). A candidate gene for this disease, HFE, was identified by positional cloning (Feder, J. N., et al. Nature Genetics 13:399-408 (1996)). The gene, a novel member of the MHC class I family, was found to have a mutation, cysteine 282→tyrosine (C282Y), in 83% of patient chromosomes (Feder, J. N., et al. Nature Genetics 13:399-408 (1996)). This mutation eliminates the ability of HFE to associate with β2-microglobulin (β2m) and prevents cell-surface expression (Feder, J. N., et al., J. Biol. Chem. 272:14025-14028 (1997)). However, the relationship of this class I-like molecule to the regulation of iron metabolism has remained obscure.
Thus, an object of the instant invention is to provide a molecular basis for the relationship of HFE to iron metabolism, and diagnostic and therapeutic agents for the treatment of iron overload diseases and iron deficiency diseases.